Podcasts about diabetes obes metab

¿Ozempic es solo para bajar de peso? La respuesta es mucho más profunda. En este video te explico, con evidencia científica clara, lo que realmente sucede en tu cuerpo cuando tomas Ozempic (semaglutida): -Cómo regula el apetito en tu cerebro -Cómo mejora tu digestión y metabolismo -Por qué reduce el "ruido de comida" -Y cómo puede devolverte el control sobre tu salud metabólica ¡Suscríbete a este podcast en tu plataforma favorita para no perderte nada!

Eileen Egan, DNP, FNP-C, BC-ADM, CDCES, FADCES joins The Huddle to share her expertise about the interplay between weight and glycemic management in people with Type 2 diabetes, the importance of meeting glycemic and weight goals early after a Type 2 diabetes diagnosis, as well as best practices for helping people stay motivated and engaged. This episode was made possible with support from Lilly, A Medicine Company. Learn more about this topic in this accompanying patient/client handout (support for the development of this handout was provided by Lilly, A Medicine Company): adces_tipsheet_early_control2.pdf References:American Diabetes Association. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes- 2024. Diabetes Care, 47(1): S145-S157.Center for Disease Control and Prevention. Adult overweight and obesity. https://www.cdc.gov/obesity/basics/adult-defining.htmlDCCT/EDIC study research group. Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up. Diabetes Care. 2016;39(5):686-693. Gregg E, Jakicic J, Blackburn G, et al. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post hoc analysis of the Look AHEAD randomized clinical trial. Lancet Diabetes Endocrinol. 2016; 4(11): 913-921.Gutiérrez-Cuevas J, Santos A, Armendariz-Borunda J. Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases. Int J Mol Sci. 2021. 27;22(21):11629.Howard BV, Ruotolo G, Robbins DC. Obesity and dyslipidemia. Endocrinol Metab Clin North Am. 2003;32(4):855-867. Jin X, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023;13(6):2403-2424.  Laiteerapong N, Ham SA, Gao Y, et al. The legacy effect in type 2 diabetes: impact of early glycemic control on future complications (The Diabetes & Aging Study). Diabetes Care. 2019;42(3):416-426.Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial.Lancet Diabetes Endocrinol. 2019;7(5):344-355.Lingvay I, Sumithran P, Cohen RV, le Roux CW. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet. 2022 Jan 22;399(10322):394-405. doi: 10.1016/S0140-6736(21)01919-X. Epub 2021 Sep 30. Erratum in: Lancet. 2022 Jan 22;399(10322):358. PMID: 34600604Rachel G. Miller, Trevor J. Orchard; Understanding Metabolic Memory: A Tale of Two Studies. Diabetes 1 March 2020; 69 (3): 291–299. https://doi.org/10.2337/db19-0514Ross, R., Neeland, I.J., Yamashita, S. et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol16, 177–189 (2020). https://doi.org/10.1038/s41574-019-0310-7Thom G, McIntosh A, Messow CM, et al. Weight loss-induced increase in fasting ghrelin concentration is a predictor of weight regain: Evidence from the Diabetes Remission Clinical Trial (DiRECT). Diabetes Obes Metab. 2021;(23):711-719.Tsai AG, Bessesen DH. Obesity. Ann Intern Med. 2019;170(5):ITC33-ITC48.Wing RR, Bolin P, Brancati FL, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145-154.World Health Organization. Obesity. https://www.who.int/health-topics/obesity#tab=tab_1 Listen to more episodes of The Huddle at adces.org/perspectives/the-huddle-podcast.Learn more about ADCES and the many benefits of membership at adces.org/join.

Autor: Luciano Giacaglia Revista: Diabetes Obes Metab. Ref: Arai T. Beneficial effect of oral semaglutide for type 2 diabetes mellitus in patients with metabolic dysfunction-associated steatotic liver disease: A prospective, multicentre, observational study. Diabetes Obes Metab. 2024 Nov;26(11):4958-4965. doi: 10.1111/dom.15898.

The Ozempic episode is HERE (Part 1). By this point, most of us have heard of the celebrities taking Ozempic/ Wegovy. If not, you must not watch the news or be on social media...lucky you! These drugs are being called "a miracle" and the "end of the ob*sity epidemic". Is this true? Abbey is joined by her intern, Nicole, to discuss all things weight loss drugs. Together they cover: what Ozempic is, how it works for diabetes and for weight loss, the difference between Ozempic and Wegovy, common side effects, and more. There's a lot of discourse in this episode, so buckle up! TW: "ob*se and ov*rweight terms are used in the episode to describe the research and BMI qualifiers. Be sure to rate the podcast and subscribe! Join the Fork Diet Culture Community! Work with Abbey 1-on-1 More about Abbey Follow on IG and TT: @fork.diet.culture Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. [Updated 2023 Jan 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551568/ Shetty R, Basheer FT, Poojari PG, Thunga G, Chandran VP, Acharya LD. Adverse drug reactions of GLP-1 agonists: A systematic review of case reports. Diabetes Metab Syndr. 2022;16(3):102427. doi:10.1016/j.dsx.2022.102427 Kapoor I, Sarvepalli SM, D'Alessio D, Grewal DS, Hadziahmetovic M. GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials. Surv Ophthalmol. 2023;68(6):1071-1083. doi:10.1016/j.survophthal.2023.07.002 Suran M. As Ozempic's Popularity Soars, Here's What to Know About Semaglutide and Weight Loss. JAMA. 2023;329(19):1627-1629. doi:10.1001/jama.2023.2438 Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725 Novo Nordisck. Ozempic. https://www.novocare.com/diabetes/products/ozempic.html Web site. Updated 2024 Gómez Lumbreras A, Tan MS, Villa-Zapata L, Ilham S, Earl JC, Malone DC. Cost-effectiveness analysis of five anti-obesity medications from a US payer's perspective. Nutr Metab Cardiovasc Dis. 2023;33(6):1268-1276. doi:10.1016/j.numecd.2023.03.012 Gordon A, Hobbs M. Maintenance Phase; Ozempic. 2023;Podcast

Welcome to our weekly live series where we discuss all topics related to kidney health, nutrition, and longevity.Timestamps00:00 Start0:30 Introduction1:15 Sodium and Kidney Disease7:12 Nanoplastics in bottled water16:09 Tirzepatide and protein in the urine23:12 Exercise and Longevity26:33 Artificial sweeteners and Gut MicrobiomeReferences:1. Sodium and CKD-World Health Organization . Guideline: Sodium Intake for Adults and Children. World Health Organization; Geneva, Switzerland: 2012. pp. 1–46.-Wright JA, Cavanaugh KL. Dietary sodium in chronic kidney disease: a comprehensive approach. Semin Dial. 2010 Jul-Aug;23(4):415-21.-Verma A, Popa C. The Interplay Between Dietary Sodium Intake and Proteinuria in CKD. Kidney Int Rep (2023) 8, 1133–11362. Nanoplastics and Health-Qian, N., et al. (2024). "Rapid single-particle chemical imaging of nanoplastics by SRS microscopy." Proceedings of the National Academy of Sciences 121(3): e2300582121.3. Tirzepatide and Proteinuria-Karakasis et al. Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis .Diabetes Obes Metab 2023 Dec 20;[EPub Ahead of Print]4. Walking and longevity-Kankaanpää A, Tolvanen A, Joensuu L, Waller K, Heikkinen A, Kaprio J, Ollikainen M, Sillanpää E. The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality - a prospective twin study. medRxiv [Preprint]. 2023 Jun 5:20235. Artificial Sweeteners and gut microbiome-Hosseini A, Barlow GM, Leite G, Rashid M, Parodi G, Wang J, Morales W, Weitsman S, Rezaie A, Pimentel M, Mathur R. Consuming artificial sweeteners may alter the structure and function of duodenal microbial communities. iScience. 2023 Nov 23;26(12):108530.VISIT OUR STOREStore: https://www.selfelements.comFOLLOW USwww.selfprinciple.orgwww. youtube.com/selfprinciplewww.youtube.com/plantbasedkidneyhealthwww.instagram.com/seanhashmimd

In this episode of Reverse the Post-Op Regain, I take a look into Ozempic, the once-weekly injectable drug that has gained popularity for weight loss. Join us as we explore how Ozempic works, its role in weight loss surgery, and its potential impact on weight regain. We'll discuss key considerations, the importance of maintaining muscle mass, and practical tips to support your weight loss journey while on this medication. Remember, individualised advice is essential, and we encourage you to consult a healthcare professional for personalised guidance. Let's navigate the road to sustainable weight management together!Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19. PMID: 35441470; PMCID: PMC9542252.Ojeniran M, Dube B, Paige A, Ton J, Lindblad AJ. Semaglutide for weight loss. Can Fam Physician. 2021 Nov;67(11):842. doi: 10.46747/cfp.6711842. PMID: 34772713; PMCID: PMC8589135.Let's chat: Work with me 1:1 by learning about my coaching: https://simpleandeasynutrition.com/apply.html Website: https://www.thebariatriccollective.com.au/ Instagram: @thebariatriccollective Facebook: https://www.facebook.com/thebariatriccollective Email: suraya@thebariatriccollective.com.au Free Downloads: Causes of Weight Regain Graphic Download a Free Three Day Meal Plan with Recipes DISCLAIMER The advice provided in the podcast is general in nature and is not intended to constitute or substitute for dietetics, nutrition, professional or medical advice. You should not rely on the information presented here as medical advice. It is important to consult a medical professional for personalised medical or dietetic advice for your specific circumstances.

Unless you've been living off-grid for the last few months, chances are you've heard of Ozempic (or semaglutide)– the newest FDA approved miracle injection for weight loss. Social media has ignited feeds across the world with weight loss transformation posts from semaglutide injections- and 812 million views on TikTok to be exact. Tailored to diabetes, this drug works by stimulating insulin secretion and therefore lowering fasting and postprandial glucose levels in four mechanisms. During the Ozempic drug trials, it was noted that weight loss was such a consistent and dramatic side effect that the FDA approved semaglutide for weight loss under the brand name Wegovy in 2021. In this episode, I discuss: The four mechanisms of Ozempic  Changes in insulin sensitivity Increased energy expenditure by encouraging stored fat to turn into energy. Slows gastric emptying The impact on appetite. And what current research is finding. (Hint: It might not be a long-term weight loss miracle!) To sum it up, weight loss medications like Ozempic cannot have substantial results without compromise (i.e. losing lean muscle mass). Most importantly, NONE of the weight loss medications are fixing the root cause of the problem. The purpose of this podcast is to help you make an informed decision about your options for weight loss. If you are considering semaglutide injections for weight loss, talk to your doctor about the pros and cons! Love it? Hate it? We'd love to hear your feedback!   References used for this episode:   1.    https://pubmed.ncbi.nlm.nih.gov/30122305/ O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649. doi:10.1016/S0140-6736(18)31773-2 2.   https://pubmed.ncbi.nlm.nih.gov/33755728/  Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.322 3.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769337/  Sargeant JA, Henson J, King JA, Yates T, Khunti K, Davies MJ. A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans. Endocrinol Metab (Seoul). 2019 Sep;34(3):247-262. doi: 10.3803/EnM.2019.34.3.247. PMID: 31565876; PMCID: PMC6769337. 4.  https://pubmed.ncbi.nlm.nih.gov/35441470/  Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725   Interested in our Lean for Life Membership? Help yourself feel aligned using our three phase approach: Lean for Life Membership called Heal, Optimize , and Refinewhere you will be empowered to reverse previous metabolic damage with the assistance of our team of Registered Dietitian Nutritionists. Check out more details on our website! Want to learn more about our one-on-one Empowered Nutrition coaching? Book a free chemistry call to discuss your story and see if we're a good fit. Enjoying the podcast? Please review the Empowered Nutrition Podcast on Apple Podcasts or wherever you listen! Then, send me a screenshot of your positive review to podcast@empowerednutrition.health as a DM on Instagram (@empowerednutrition.health).Include a brief description of what you're working on with your health and/or nutrition and I'll send you a free custom meal plan! Do you have questions you would like answered on the Empowered Nutrition podcast? You can propose your questions/ideas here or reach out to me at podcast@empowerednutrition.health Follow us on: Facebook | Instagram | Pinterest        

Disclaimer This podcast is for educational purposes only not intended to treat cure diagnose or prevent sickness illness disease or mental health issues if you are making any lifestyle changes to your health and wellness routine for yourself and family consult with your medical doctor first. Reference: Tian J, Jin D, Bao Q, Ding Q, Zhang H, Gao Z, Song J, Lian F, Tong X. Evidence and potential mechanisms of traditional Chinese medicine for the treatment of type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2019 Aug;21(8):1801-1816. doi: 10.1111/dom.13760. Epub 2019 Jun 17. PMID: 31050124. #Holisticmedicine #alternativemedicine #alternativehealth #alternativehealing #herbs #type2diabetes #holistichealing #holistichealth #Chinesemedicine --- Send in a voice message: https://anchor.fm/rdlc/message

Post przerywany (z j. ang. Intermittent fasting, w skrócie IF) to model żywieniowy nabierający coraz większej popularności. Ma poprawiać zdrowie i być niezawodnym sposobem na szczupłą sylwetkę. Ale o co chodzi i ile w tym prawdy? Dla kogo IF nadaje się idealnie, a kto powinien uważać? O wszystkim tym opowiadam w odcinku. Dowiesz się z niego także czym jest chronożywienie oraz co na temat IF mówi nauka, ponieważ odcinek przygotowałam w oparciu o kilkanaście prac naukowych. Zapraszam do wysłuchania!Mój Instagram: https://www.instagram.com/fit_gruszecka/ Mój Facebook: https://www.facebook.com/KarolinaGruszeckaDietetyk/ Moja grupa na FB Clean eating by Gruszecka: https://www.facebook.com/groups/1008891972485382/Źródła:1. Goo RH, Moore JG, Greenberg E, Alazraki NP. Circadian variation in gastric emptying of meals in humans. Gastroenterology. 1987;93(3):515-518.2. Qian, J, Dalla Man, C, Morris, CJ, Cobelli, C, Scheer, FAJL. Differential effects of the circadian system and circadian misalignment on insulin sensitivity and insulin secretion in humans. Diabetes Obes Metab. 2018; 20: 2481– 2485.3. Morris CJ, Garcia JI, Myers S, Yang JN, Trienekens N, Scheer FA. The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis. Obesity (Silver Spring). 2015;23(10):2053-2058.4. Morris CJ, Garcia JI, Myers S, Yang JN, Trienekens N, Scheer FA. The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis. Obesity (Silver Spring). 2015;23(10):2053-2058.5. J Qian, R Caputo, C J Morris, W Wang, F A Scheer, 0041 Circadian Misalignment Increases The Desire For Food Intake In Chronic Shift Workers, Sleep, Volume 41, Issue suppl_1, April 2018, Page A17.6. Munsters MJ, Saris WH. Effects of meal frequency on metabolic profiles and substrate partitioning in lean healthy males., PLoS One. 2012;7(6):e38632.7. Ohkawara K, Cornier MA, Kohrt WM, Melanson EL. Effects of Increased Meal Frequency on Fat Oxidation and Perceived Hunger. Obesity (Silver Spring). 2013 Feb;21(2):336-43.6. Leidy HJ, Campbell WW. The effect of eating frequency on appetite control and food intake: brief synopsis of controlled feeding studies., J Nutr. 2011 Jan;141(1):154-7.7. Perrigue MM, Drewnowski A, Wang CY, Neuhouser ML. Higher Eating Frequency Does Not Decrease Appetite in Healthy Adults. J Nutr. 2016 Jan;146(1):59-64.8. Alhamdan BA, Garcia-Alvarez A, Alzahrnai AH, et al. Alternate-day versus daily energy restriction diets: which is more effective for weight loss? A systematic review and meta-analysis. Obes Sci Pract. 2016;2(3):293-302. 9. Sutton EF i wsp. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab. 2018 Jun 5;27(6):1212-1221.e3. 10. Harris L, McGarty A, Hutchison L, Ells L, Hankey C. Short-term intermittent energy restriction interventions for weight management: a systematic review and meta-analysis. Obes Rev. 2018;19(1):1-13. 11. Headland M, Clifton PM, Carter S, Keogh JB. Weight-loss outcomes: A systematic review and meta-analysis of intermittent energy restriction trials lasting a minimum of 6 months. Nutrients. 2016;8(6).

O uso de chás emagrecedores é muito difundido na população e é inclusive prescrito por alguns médicos. Mas o que a ciência tem a dizer sobre esses compostos? Neste episódio discuto uma revisão sistemática com metanálise publicada em 2020 que avaliou a eficácia de diversas plantas medicinais com relação a perda de peso em pessoas com sobrepeso ou obesidade. Ouça o episódio até o final e descubra os resultados dessa revisão. Siga: @endodirect Referência: Maunder A, Bessell E, Lauche R, Adams J, Sainsbury A, Fuller NR. Effectiveness of herbal medicines for weight loss: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020 Jun;22(6):891-903. doi: 10.1111/dom.13973. Epub 2020 Feb 15. PMID: 31984610.

A 5-minute summary of a randomized controlled trial comparing the effects of a short-acting vs. long-acting GLP-1 receptor agonist on food intake, appetite and exocrine pancreas function, published in Diabetes, Obesity & Metabolism. Listen for a quick overview of the key findings. Publication: Quast DR, et al. Macronutrient intake, appetite, food preferences and exocrine pancreas function after treatment with short- and long-acting glucagon-like peptide-1 receptor agonists in type 2 diabetes. Diabetes Obes Metab. 2021 Oct;23(10):2344-2353. Additional references: Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012 Dec;8(12):728-42. For more free education, visit the DKIP website, follow us on Twitter (@dkipractice) or connect on LinkedIn. Funding statement: This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education.

A 5-minute summary of an observational study investigating how glucose control affected the immune response to COVID-19 vaccination, published in Diabetes, Obesity & Metabolism. Listen for a quick overview of the key findings. Publication: Marfella R, et al. Does poor glycaemic control affect the immunogenicity of the COVID-19 vaccination in patients with type 2 diabetes: The CAVEAT study. Diabetes Obes Metab. 2021 Sep 8. doi: 10.1111/dom.14547. Epub ahead of print. Additional references: Rawshani A, et al. Severe COVID-19 in people with type 1 and type 2 diabetes in Sweden: A nationwide retrospective cohort study. Lancet Reg Health Eur. 2021 May;4:100105. doi: 10.1016/j.lanepe.2021.100105. Epub 2021 Apr 30. For more free education, visit the DKIP website, follow us on Twitter (@dkipractice) or connect on LinkedIn. Funding statement: This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education.

Hear a 5-minute summary of a small study investigating whether the GLP-1 receptor agonist liraglutide affected diastolic function in people with type 2 diabetes, presented at ESC 2021 and later published Diabetes, Obesity and Metabolism. Listen for a quick overview of the key findings. Publication: Bojer AS, et al. Metabolic improvement with short-term, glucagon-like peptide-1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2021 Oct;23(10):2374-2384. doi: 10.1111/dom.14480. Epub 2021 Jul 26. For more free education, visit the DKIP website, follow us on Twitter (@dkipractice) or connect on LinkedIn. This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education.

中国药监局 批准我国自主研发的长效GLP-1受体激动剂治疗2型糖尿病Cell子刊 4小时和6小时限时进食对体重和心血管代谢健康的影响Diabetes Obesity & Metabolism 严重低血糖与心血管事件发现的关系Gut 地中海饮食通过肠道菌群影响肥胖患者的胆固醇水平，不受能量的影响Nature子刊 光遗传学技术刺激脂肪产热来预防肥胖聚乙二醇洛塞那肽注射液（polyethylene glycol loxenatide）聚乙二醇洛塞那肽注射液（PEX168）是一种新型的、我国自主研发的、长效胰高血糖素样肽-1（GLP-1）受体激动剂，可促进葡萄糖依赖的胰岛素分泌，配合饮食控制和运动，单药或与二甲双胍联合，用于改善成人2型糖尿病患者的血糖控制。2019年5月中国国家药品监督管理局批准聚乙二醇洛塞那肽注射液上市，用于治疗2型糖尿病。《随机对照研究：聚乙二醇洛塞那肽注射液单药治疗中国人群2型糖尿病的疗效和安全性的3a期临床研究》Diabetes Obesity and Metabolism，2020年12月 (1)研究目的是评价聚乙二醇洛塞那肽注射液单药治疗中国2型糖尿病的疗效和安全性。这项多中心的、随机的、双盲的、安慰剂对照的3a期临床试验中，来自中日友好医院的研究人员招募了361名、糖化血红蛋白7.0%-10.5%、空腹血糖

中国药监局 批准我国自主研发的长效GLP-1受体激动剂治疗2型糖尿病Cell子刊 4小时和6小时限时进食对体重和心血管代谢健康的影响Diabetes Obesity & Metabolism 严重低血糖与心血管事件发现的关系Gut 地中海饮食通过肠道菌群影响肥胖患者的胆固醇水平，不受能量的影响Nature子刊 光遗传学技术刺激脂肪产热来预防肥胖聚乙二醇洛塞那肽注射液（polyethylene glycol loxenatide）聚乙二醇洛塞那肽注射液（PEX168）是一种新型的、我国自主研发的、长效胰高血糖素样肽-1（GLP-1）受体激动剂，可促进葡萄糖依赖的胰岛素分泌，配合饮食控制和运动，单药或与二甲双胍联合，用于改善成人2型糖尿病患者的血糖控制。2019年5月中国国家药品监督管理局批准聚乙二醇洛塞那肽注射液上市，用于治疗2型糖尿病。《随机对照研究：聚乙二醇洛塞那肽注射液单药治疗中国人群2型糖尿病的疗效和安全性的3a期临床研究》Diabetes Obesity and Metabolism，2020年12月 (1)研究目的是评价聚乙二醇洛塞那肽注射液单药治疗中国2型糖尿病的疗效和安全性。这项多中心的、随机的、双盲的、安慰剂对照的3a期临床试验中，来自中日友好医院的研究人员招募了361名、糖化血红蛋白7.0%-10.5%、空腹血糖

For over a century, the treatments and technologies used to treat diabetes have evolved. New tools are now available to aid in diabetes management and to help patients further manage and better control their glucose levels. 1,2 Through their recently announced collaboration, Dexcom and Lilly are at the forefront of enhancing diabetes care. 3 In this episode Dr. Chad Worz and guest speakers Deirdre Ibsen and Dr. Thomas Blevins discuss these important technological and therapeutic achievements over time, as well as 2 products available from Dexcom and Lilly and how they may benefit patients with diabetes. References:  Dexcom G6 Pro User Guide. https://dexcompdf.s3-us-west-2.amazonaws.com/Dexcom-G6-Pro-User-Guide.pdf. Accessed October 12, 2020. Lyumjev [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC. Eli Lilly and Company. Lilly and Dexcom team up on new program to help improve diabetes management. https://provider.dexcom.com/products/dexcom-g6-pro/training-resources. Accessed October 12, 2020. Centers for Disease Control. National Diabetes Statistics Report 2020 Estimates of Diabetes and Its Burden in the United States. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed October 1, 2020. American Diabetes Association. Diabetes and Quality of Life. http://journal.diabetes.org/diabetesspectrum/00v13n1/pg48.htm. Accessed October 1, 2020. American Diabetes Association. Caring for the Caregiver. https://spectrum.diabetesjournals.org/content/17/1/37.full-text.pdf. Accessed October 15, 2020. Ali MK, Bullard KM, Gregg EW. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med. 2013;369(3):287-288. Foster NC, Beck RW, Miller KM, et al. State of type 1 diabetes management and outcomes from the T1D Exchange in 2016-2018. Diabetes Technol Ther. 2019;21(2):66-72. American Diabetes Association. 7. Diabetes Technology: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(suppl 1):S77-S88. Hirsch IB. History of Glucose Monitoring. https://professional.diabetes.org/sites/professional.diabetes.org/files/media/db201811.pdf. Accessed October 1, 2020. White JR. A brief history of the development of diabetes medications. Diabetes Spectr. 2014;27(2):82-86. Science History Institute. Frederick Banting, Charles Best, James Collip, and John Macleod. https://www.sciencehistory.org/historical-profile/frederick-banting-charles-best-james-collip-and-john-macleod. Accessed October 1, 2020. American Diabetes Association. Timeline. https://www.diabetes.org/resources/timeline. Accessed October 9, 2020. Humalog [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC. Selam J-L. Evolution of diabetes insulin delivery devices. J Diabetes Sci Technol. 2010;4(3):505-513. American Association of Diabetes Educators. Insulin Injection Know-How. https://www.diabeteseducator.org/docs/default-source/legacy-docs/_resources/pdf/general/Insulin_Injection_How_To_AADE.pdf. Accessed October 1, 2020. Hyllested-Winge J, Jensen KH, Rex J. A review of 25 years' experience with the NovoPen® family of insulin pens in the management of diabetes mellitus. Clin Drug Investig. 2010;30(10):643-674. Eli Lilly and Company. Lilly Launches KwikPen(TM) for Humalog(R) and Humalog Mixtures [press release]. https://investor.lilly.com/news-releases/news-release-details/lilly-launches-kwikpentm-humalogr-and-humalog-mixtures. Accessed October 12, 2020. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(suppl 1):S66-S76. Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. Fonseca VA, Grunberger G, Anhalt H, et al. Continuous glucose monitoring: a consensus conference of the American Association of Clinical Endocrinologists and American College of Endocrinology. Endocr Pract. 2016;22(8):1008-1021. Battelino T, Danne T, Bergenstal RM, et al. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diabetes Care. 2019;42(8):1593-1603. Dexcom G6 Pro Unblinded Patient Guide. https://dexcompdf.s3-us-west-2.amazonaws.com/Dexcom-G6-Pro-Unblinded-Patient-Guide.pdf. Accessed October 12, 2020. Dexcom Announces FDA Clearance of New Dexcom G6 Pro CGM. https://provider.dexcom.com/industry-news/fda-authorizes-dexcom-g6-pro. Accessed October 2, 2020. Beck RW, Riddlesworth T, Ruedy K, et al. Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial. 2017;317(4):371-378. Beck RW, Riddlesworth TD, Ruedy K, et al. Continuous glucose monitoring versus usual care in patients with type 2 diabetes receiving multiple daily insulin injections: a randomized trial. Ann Intern Med. 2017;167(6):365-374. Polonsky WH, Hessler D, Ruedy KJ, Beck RW. The impact of continuous glucose monitoring on markers of quality of life in adults with type 1 diabetes: further findings from the DIAMOND randomized clinical trial. Diabetes Care. 2017;40(6):736-741. Pratley RE, Kanapka LG, Rickels MR, et al. Effect of continuous glucose monitoring on hypoglycemia in older adults with type 1 diabetes: a randomized clinical trial. 2020;323(23):2397-2406. Ruedy KJ, Parkin CG, Riddlesworth TD, Graham C. Continuous glucose monitoring in older adults with type 1 and type 2 diabetes using multiple daily injections of insulin: results from the DIAMOND trial. J Diabetes Sci Technol. 2017;11(6):1138-1146. Lind M, Polonsky W, Hirsch IB, et al. Continuous glucose monitoring vs conventional therapy for glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections: the GOLD randomized clinical trial. 2017;317(4):379-387. Frequently Asked Questions. https://provider.dexcom.com/products/dexcom-g6-pro/faqs. Accessed October 15, 2020. Dexcom Products: Dexcom G6 Pro. https://provider.dexcom.com/products/professional-cgm. Accessed October 15, 2020. How to Customize Alarm and Alerts. https://www.dexcom.com/faqs/how-to-customize-alarm-and-alerts. Accessed October 15, 2020. Trend Arrows and Treatment Decisions. https://s3-us-west-2.amazonaws.com/dexcompdf/HCP_Website/LBL015804+G6+Trend+Arrows+and+Treatment+Decisions.pdf. Accessed October 15, 2020. Why CGM? https://provider.dexcom.com/why-cgm. Accessed October 12, 2020. Pharmacy Coverage. https://provider.dexcom.com/pharmacy-coverage. Accessed October 12, 2020. Is There Reimbursement for Using Dexcom G6 Pro? https://provider.dexcom.com/faqs/there-reimbursement-using-dexcom-g6-pro. Accessed October 12, 2020. Hypoglycemia Unawareness. https://provider.dexcom.com/education-research/clinical-evidence/clinical-studies/real-time-continuous-glucose-monitoring-cgm. Accessed October 15, 2020. Garg SK, Wernicke-Panten K, Wardecki M, et al. Safety, immunogenicity, and glycemic control of insulin aspart biosimilar SAR341402 versus originator insulin aspart in people with diabetes also using insulin glargine: 12-month results from the GEMELLI 1 trial. Diabetes Technol Ther. 2020;22(7):516-526. Dexcom G6 Pro Blinded Patient Guide. https://dexcompdf.s3-us-west-2.amazonaws.com/HCP_Website/Dexcom+G6+Pro+Resources/LBL017177+Rev+004+Artwork%2C+Dexcom+G6+Pro+Blinded+Patient+Guide+US_r5_WEB.pdf. Accessed November 24, 2020. Dexcom CLARITY Diabetes Management Software. https://www.dexcom.com/clarity. Accessed May 15, 2020. Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized double-blind clinical trial comparing ultra rapid lispro with lispro in a basal-bolus regimen in patients with type 2 diabetes: PRONTO-T2D. Diabetes Care. Published online July 2, 2020. doi: 10.2337/dc19-2550. Klaff L, Cao D, Dellva MA, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. 2020;22(10):1799-1807. See omnystudio.com/listener for privacy information. Learn more about your ad choices. Visit megaphone.fm/adchoices

FDA 批准超速效赖脯胰岛素治疗糖尿病Diabetes Care 1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖Nature Review Cardiology SGLT2抑制剂：除血糖控制外的心血管益处机制Annals of Internal Medicine SGLT2抑制剂与糖尿病酮症酸中毒风险Cell ALK基因功能下调可以减肥超速效赖脯胰岛素（URLi）超速效赖脯胰岛素（URLi），在短效赖脯胰岛素的基础上改良的一种起效更快、持续时间更短的胰岛素，更大程度上模拟生理条件下、餐后胰岛素的释放曲线。超速效赖脯胰岛素与赖脯胰岛素相比，达到50%最大功效的时间分别为12.8分钟和25.4分钟，两者30分钟内的总暴露量分别为99.3pmol*h/L和34.8pmol*h/L。超速效赖脯胰岛素20分钟达到峰值，持续6小时。2020年6月，超速效赖脯胰岛素（LyumjevTM）已经被FDA批准上市。《PRONTO-T2D研究：超速效赖脯胰岛素与赖脯胰岛素在长效胰岛素基础上治疗2型糖尿病的3期临床研究》Diabetes Care，2020年6月 (1)评价赖脯胰岛素与超速效赖脯胰岛素（URLi）比较，在长效胰岛素基础上治疗2型糖尿病的疗效和安全性。共673位患者，在优化的、长效甘精胰岛素或长效德谷胰岛素的基础上，联合餐前赖脯胰岛素治疗8周后，患者随机分入餐前0-2分钟注射超速效赖脯胰岛素组、或普通赖脯胰岛素组。两种短效胰岛素均能改善患者糖化血红蛋白，治疗结束时糖化血红蛋白分别为6.92%和6.86%。在控制1小时和2小时餐后血糖的变化方面，超速效赖脯胰岛素优于赖脯胰岛素：餐后1小时两组差异为0.66 mmol/L，2小时两组差异为0.96 mmol/L。接受超速效赖脯胰岛素治疗的患者餐后30分钟至4.0小时内，餐后血糖偏移明显减少。两种治疗方法之间的总体治疗紧急不良事件，包括低血糖，发生率相似。结论：在2型糖尿病患者中，餐时注射的超速效赖脯胰岛素与餐前注射的赖脯胰岛素在控制糖化血红蛋白方面效果相当，但在餐后血糖控制方面优于赖脯胰岛素。《PRONTO-T1D研究：与赖脯胰岛素相比，超速效赖脯胰岛素改善了1型糖尿病患者餐后血糖控制》Diabetes Obesity Metabolism，2020年8月 (2)在一项为期26周的III期临床试验中，评估了超速效赖脯胰岛素（URLi）与赖脯胰岛素在成人1型糖尿病患者中的疗效和安全性。研究发现超速效赖脯胰岛素在控制糖化血红蛋白方面，不劣于赖脯胰岛素。餐时注射超速效赖脯胰岛素在减少餐时1小时和2小时餐后血糖方面明显更优秀：1小时两组血糖差异为1.55mmol/L， 2小时两组差异为1.73 mmol/L，餐后4小时低血糖发作降低37%（P = 0.013）。其他的不良反应发生率相似。结论：在1型糖尿病中，超速效赖脯胰岛素提供了良好的血糖控制，餐后血糖控制优于赖脯胰岛素。1型糖尿病的运动管理规律的运动对1型糖尿病儿童和青少年具有重要的健康和社交益处，应鼓励。有氧运动（步行、骑车）通常可降低血糖浓度，而无氧运动（全速跑、曲棍球、举重）通常会升高血糖，许多团体运动（足球、篮球、棒球）包含有氧和无氧运动。低血糖可能发生在运动期间或运动后不久，或者延迟至运动后数小时或睡眠时。高血糖可能发生在运动期间，或情绪激动时。建议运动前、运动30分钟、运动恢复期和睡前监测血糖。《1型糖尿病运动后血糖控制与残留的β细胞功能有关》Diabetes Care，2020年10月 (3)研究旨在评价剩余β细胞功能对1型糖尿病患者运动后血糖的影响。研究招募30名、1型糖尿病病史≥3年的参与者，首先盲法进行7天的自由生活数据采集；然后进行3小时混合餐试验评估C肽和胰高血糖素水平。使用C肽峰值将参与者分成极低C肽组（C肽浓度200 pmol/L）；最后，参与者完成45分钟在60%VO2峰值的运动，然后再进行48小时的连续血糖检测。在运动后12小时和24小时，高C肽组参与者中葡萄糖正常的时间显著高于其他两组的参与者（高C肽组：12小时 73.5%，24 h 76.3%；低C肽组：12小时43.6%，24小时52.3%；极低C肽组12小时40.6%，24小时 51.3%）。而且，高C肽组参与者中高血糖的时间显著低于其他两组，血糖的波动也更小（P < 0.01）。从运动前到运动后24小时连续血糖检测的结果发现：高C肽组的参与者血糖控制得更好了（正常血糖的时间增加了12.1%），但另外两组的血糖控制得更差了（正常血糖的时间减少了9.1%和16.2%）。结论：剩余的β细胞功能可能部分解释了1型糖尿病患者运动后血糖的个体间差异，量化C肽有助于为患者提供个性化、针对性的运动支持。《1型糖尿病与有氧运动：在长效基础胰岛素基础上，运动前单次口服果糖可降低运动性低血糖的风险》Diabetes Care，2020年8月 (4)虽然调整胰岛素是降低1型糖尿病患者运动相关性低血糖风险的既定策略，但对超长效基础胰岛素治疗的患者来说，这并不容易实现。目前的研究确定了1型糖尿病患者在运动前摄入果糖是否能降低因运动引起的低血糖的风险。研究中14名参与分别完成了两次60min的有氧自行车运动，一次在运动前30min服用20g果糖，一次不服用果糖。摄入果糖的情况下，患者60min平均只发生1次低血糖事件，而对照组在运动的约30分钟内发生6次低血糖事件，果糖将运动时低血糖的风险降低了87.8%。服用果糖的运动期间平均血糖为7.3mmol/L，对照组为5.5mmol/L。摄取果糖后30分钟内休息时，患者的乳酸水平较高，但运动期间即回到基线。结论：对于使用超长效胰岛素的1型糖尿病患者而言，运动前摄取果糖是一种简单可行、有效且耐受良好的策略，可以减轻运动引起的低血糖风险，同时避免高血糖。《1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖》Diabetes Care，2020年8月 (5)1型糖尿病中，心率变异性（HRV）降低可能是早期的自主神经功能障碍的一种表现；1型糖尿病患者，尤其是剧烈运动和长时间运动时，血糖会急剧变化，从而对心率变异性产生负面影响。本研究中，20名患有1型糖尿病的业余运动员9天骑行1500公里。研究出乎意料的发现，骑行的距离越长，高血糖时间越长，低血糖时间越短，同时夜间心率变异性越低；这可能和副交感神经张力降低有关。而且在这一过程中，胰岛素的使用没有改变，从饮食中摄入的碳水化合物也没有变化减少。结论：在患有1型糖尿病的运动爱好者中，长时间中高强度运动加重了高血糖，而高血糖与副交感神经及心脏功能相关；考虑潜在的对心脏的有害后果，未来的工作应该集中在理解和管理运动引起的高血糖现象。《1型糖尿病与中高强度运动：在运动前，采用长效胰岛素和胰岛素泵混合方案》Lancet Diabetes & Endocrinology，2020年6月 (6)使用持续皮下注射胰岛素泵（CSII）的1型糖尿病患者通常会在长时间运动前移除泵，但这种方法可能会增加高血糖和酮症的风险。该研究目的是评估一种混合方法的有效性和安全性，即通过胰岛素泵混合德谷胰岛素qd（一种长效胰岛素）提供每日必须的基础胰岛素治疗。这是一个单中心、开放标签、概念验证、随机交叉试验中，招募了平时规律使用胰岛素泵的1型糖尿病患者，开放标签分入单用胰岛素泵组和胰岛素泵联合长效胰岛素治疗组中，两组患者均在运动前60分钟停止胰岛素泵，运动后立即重新连接。与通常的胰岛素泵方案相比，混合胰岛素泵方案的参与者在中高强度运动后6小时内，血糖稳定（4-10mmol/L）的时间显著延长；在家运动时的高血糖持续时间更短。两种干预措施低血糖时间和低血糖事件方面没有显著差异。结论：清晨注射一次长效胰岛素和胰岛素泵的混合方案似乎对有规律运动习惯的1型糖尿病成人更加安全有效的。小羽点评：1型糖尿病病患者的残余β细胞功能和自主神经功能障碍均会影响患者运动后的血糖。β细胞残余功能越差，血糖波动越大；长时间中高强度的运动，副交感神经张力降低，引发高血糖。为了更高的减少运动后高血糖，可以采用长效胰岛素和胰岛素泵混合方案；为了减少运动相关低血糖时间，可以在运动前服用果糖。2型糖尿病的药物治疗-SGLT2抑制剂钠-葡萄糖协同转运蛋白2（SGLT2）表达于肾近端小管，介导约90%的滤过葡萄糖的重吸收。SGLT2抑制剂促进肾脏对葡萄糖的排泄，因此可降低血糖、降低血压和体重，通常不会导致低血糖。SGLT2最常见的副作用为外阴阴道假丝酵母菌感染及低血压。对于合并糖尿病肾病、心力衰竭和冠心病的患者，可考虑优先使用。在《内分泌科星期五 Episode 5》中，我们聊到了SGLT2抑制剂在1型糖尿病患者中的应用，不知道各位听众是否还记得。由于SGLT2抑制剂有增加1型糖尿病患者酮症酸中毒的风险，因此欧洲仅批准了SGTL2抑制剂用于BMI>27kg/m2的1型糖尿病患者。《队列研究：SGLT2抑制剂与糖尿病酮症酸中毒风险》Annals of Internal Medicine，2020年9月 (7)研究旨在评估SGLT-2抑制剂与DPP-4抑制剂相比，是否增加2型糖尿病患者酮症酸中毒的风险。研究纳入20757名新使用SGLT-2抑制剂的患者和20757名新使用DPP-4抑制剂的患者。在370 454人年的随访中，共发生了521例酮症酸中毒。与DPP-4抑制剂相比，SGLT-2抑制剂与酮症酸中毒风险增加相关。其中，达格列净的风险比为1.86；恩格列净的风险比为2.52；卡格列净的风险比3.58。这种关联性与年龄和性别无关，在曾接受过胰岛素治疗的人群中，这种风险风险似乎更低。结论：SGLT-2抑制剂使用后酮症酸中毒风险增加近3倍，不同药物的风险比略有不同。《SGLT2抑制剂：除血糖控制外的心血管益处机制》Nature Review Cardiology，2020年7月(8)SGLT2抑制剂除了控制血糖，也可以改善心血管和肾脏结局，且获益扩展到有射血分数降低的心功能不全的非糖尿病患者中。其中的机制可能包括：（1）早期尿钠与血浆体积减少、随之而来的血细胞比积升高、血管功能改善、血压降低和组织钠的变化都可能发挥作用；（2）减少脂肪组织介导的炎症反应和炎性细胞因子的生产，心脏和肾脏转向酮体代谢，减少氧化应激，降低尿酸，减少肾小球渗透压和蛋白尿，抑制晚期糖基化产物生成。《EMPEROR-Reduce研究：恩格列净治疗心衰患者的心血管和肾脏结局》New England Journal of Medicine，2020年8月 (9)这项双盲试验中，随机分配3730名II、III或IV型心衰、射血分数≤40%的患者，除推荐治疗外，随机接受恩格列净10mg qd或安慰剂治疗。随访16个月，恩格列净组和安慰剂组中，主要终点事件（心血管死亡和心衰住院）的发生率分别为19.4%和24.7%（风险比0.75，P < 0.001）。无论是否患有糖尿病，结果是一致的。两组中肾小球滤过率下降的幅度分别为-0.55ml/min和-2.28ml/min（P < 0.001）。应用恩格列净无并发症的生殖道感染发生率更高。结论：无论是否合并糖尿病，射血分数≤40%的心力衰竭患者加用恩格列净可以降低心血管死亡或心衰住院的风险。《DECLARE-TIMI 58研究的探索性分析：达格列净与2型糖尿病患者的心脏、肾脏和四肢的预后的关系》Circulation，2020年8月 (10)有研究显示SGLT2抑制剂增加2型糖尿病的截肢的风险。在这项探索性分析中，纳入了DECLARE-TIMI 58研究中的、17 160例2型糖尿病患者，6%患有外周动脉疾病PAD。主要疗效结果为MACE(心血管[CV]死亡、心肌梗死、卒中)、CV死亡/HHF和肾脏疾病进展。截肢、外周血管重建和肢体缺血不良事件由盲的审稿人进行现场报道和分类。患有外周动脉疾病的患者，死亡、心肌梗死、卒中（风险比1.23）、心血管死亡、心衰住院（风险比1.60）、肾脏疾病进展（风险比1.60）和截肢（风险比8.37）的风险显著升高。无论是否患有外周动脉疾病，服用达格列净后，心血管死亡、心衰在入院的相对风险均降低（风险比 0.86和0.82，p=0.79），肾脏疾病进展相对风险也降低（风险比0.78和0.76，P=0.84）。随访过程中，共记录到了560例患者的肢体缺血事件、和407例截肢事件。总体而言，使用达格列净与安慰剂相比，肢体缺血不良事件和截肢的风险没有统计学差异（风险比1.07和1.09）。结论：有外周动脉疾病的患者发生心血管死亡、心衰入院和肾脏结局的风险更高，使用达格列净能够获益；但与肢体缺血不良事件没有显著相关性。《VERTIS CV研究：埃格列净对2型糖尿病、冠心病患者的心血管事件结局的影响》New England Journal of Medicine，2020年9月 (11)这项多中心、双盲试验中，随机将8246名患有2型糖尿病和冠心病的患者，分配至埃格列净5mg qd、埃格列净15mg qd或安慰剂组。平均随访3年半，埃格列净组和安慰剂组均有11.9%的患者出现了不良心血管事件。埃格列净组和安慰剂组，分别有8.1%和9.1%的参与者死于心血管疾病或因心衰恶化住院（P=0.11），肾脏原因死亡、肾脏替代治疗或肌酐水平上升2倍的发生率也没有统计学差异。结论：在患有2型糖尿病和动脉粥样硬化性心血管疾病的患者中，埃格列净在主要不良心血管事件方面并不逊于安慰剂。胖基因《基础研究：在瘦的人群中定义ALK基因》Cell，2020年6月 (12)为研究肥胖的遗传易感性，但我们对健康的瘦的人群（BMI值最低的6个百分位数）进行了全基因组关联分析研究（GWAS），发现间变性淋巴瘤激酶（ALK）是一个候选的“瘦”基因。下丘脑神经元中的表达的ALK，通过交感神经对脂肪组织分解作用的影响，来控制能量的消耗。ALK突变可以增强机体的分解代谢能力，从而有效抵抗体重增加。在果蝇中，RNAi介导的ALK基因敲除，可以降低甘油三酯水平。在小鼠中，ALK基因缺失导致瘦的动物对饮食诱导的肥胖、和瘦素突变诱导的肥胖，均具有显著的抵抗能力。结论：这项遗传和机制实验确定ALK是一个胖基因，参与抵抗体重增加。小羽点评：ALK抑制剂已经用于癌症的治疗了。如果在可以关闭ALK或使ALK基因功能下调，那么是否能够帮助我们保持苗条，甚至减重呢？参考文献1.Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D. Diabetes Care. 2020.2.Klaff L, Cao D, Dellva MA, Tobian J, Miura J, Dahl D, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. 2020.3.Taylor GS, Smith K, Capper TE, Scragg JH, Bashir A, Flatt A, et al. Postexercise Glycemic Control in Type 1 Diabetes Is Associated With Residual β-Cell Function. Diabetes Care. 2020;43(10):2362-70.4.Kosinski C, Herzig D, Laesser CI, Nakas CT, Melmer A, Vogt A, et al. A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study. Diabetes Care. 2020.5.Lespagnol E, Bocock O, Heyman J, Gamelin FX, Berthoin S, Pereira B, et al. In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in a State of Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability. Diabetes Care. 2020.6.Aronson R, Li A, Brown RE, McGaugh S, Riddell MC. Flexible insulin therapy with a hybrid regimen of insulin degludec and continuous subcutaneous insulin infusion with pump suspension before exercise in physically active adults with type 1 diabetes (FIT Untethered): a single-centre, open-label, proof-of-concept, randomised crossover trial. Lancet Diabetes Endocrinol. 2020;8(6):511-23.7.Douros A, Lix LM, Fralick M, Dell'Aniello S, Shah BR, Ronksley PE, et al. Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Ann Intern Med. 2020;173(6):417-25.8.Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020.9.Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. New England Journal of Medicine. 2020;383(15):1413-24.10.Bonaca MP, Wiviott SD, Zelniker TA, Mosenzon O, Bhatt DL, Leiter LA, et al. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58. Circulation. 2020;142(8):734-47.11.Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-35.12.Orthofer M, Valsesia A, Magi R, Wang QP, Kaczanowska J, Kozieradzki I, et al. Identification of ALK in Thinness. Cell. 2020;181(6):1246-62 e22.

For over a century, the treatments and technologies used to treat diabetes have evolved. New tools are now available to aid in diabetes management and to help patients further manage and better control their glucose levels. 1,2 Through their recently announced collaboration, Dexcom and Lilly are at the forefront of enhancing diabetes care. 3 In this episode Dr. Chad Worz and guest speakers Deirdre Ibsen and Dr. Thomas Blevins discuss these important technological and therapeutic achievements over time, as well as 2 products available from Dexcom and Lilly and how they may benefit patients with diabetes. References:  Dexcom G6 Pro User Guide. https://dexcompdf.s3-us-west-2.amazonaws.com/Dexcom-G6-Pro-User-Guide.pdf. Accessed October 12, 2020. Lyumjev [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC. Eli Lilly and Company. Lilly and Dexcom team up on new program to help improve diabetes management. https://provider.dexcom.com/products/dexcom-g6-pro/training-resources. Accessed October 12, 2020. Centers for Disease Control. National Diabetes Statistics Report 2020 Estimates of Diabetes and Its Burden in the United States. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed October 1, 2020. American Diabetes Association. Diabetes and Quality of Life. http://journal.diabetes.org/diabetesspectrum/00v13n1/pg48.htm. Accessed October 1, 2020. American Diabetes Association. Caring for the Caregiver. https://spectrum.diabetesjournals.org/content/17/1/37.full-text.pdf. Accessed October 15, 2020. Ali MK, Bullard KM, Gregg EW. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med. 2013;369(3):287-288. Foster NC, Beck RW, Miller KM, et al. State of type 1 diabetes management and outcomes from the T1D Exchange in 2016-2018. Diabetes Technol Ther. 2019;21(2):66-72. American Diabetes Association. 7. Diabetes Technology: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(suppl 1):S77-S88. Hirsch IB. History of Glucose Monitoring. https://professional.diabetes.org/sites/professional.diabetes.org/files/media/db201811.pdf. Accessed October 1, 2020. White JR. A brief history of the development of diabetes medications. Diabetes Spectr. 2014;27(2):82-86. Science History Institute. Frederick Banting, Charles Best, James Collip, and John Macleod. https://www.sciencehistory.org/historical-profile/frederick-banting-charles-best-james-collip-and-john-macleod. Accessed October 1, 2020. American Diabetes Association. Timeline. https://www.diabetes.org/resources/timeline. Accessed October 9, 2020. Humalog [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC. Selam J-L. Evolution of diabetes insulin delivery devices. J Diabetes Sci Technol. 2010;4(3):505-513. American Association of Diabetes Educators. Insulin Injection Know-How. https://www.diabeteseducator.org/docs/default-source/legacy-docs/_resources/pdf/general/Insulin_Injection_How_To_AADE.pdf. Accessed October 1, 2020. Hyllested-Winge J, Jensen KH, Rex J. A review of 25 years’ experience with the NovoPen® family of insulin pens in the management of diabetes mellitus. Clin Drug Investig. 2010;30(10):643-674. Eli Lilly and Company. Lilly Launches KwikPen(TM) for Humalog(R) and Humalog Mixtures [press release]. https://investor.lilly.com/news-releases/news-release-details/lilly-launches-kwikpentm-humalogr-and-humalog-mixtures. Accessed October 12, 2020. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(suppl 1):S66-S76. Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. Fonseca VA, Grunberger G, Anhalt H, et al. Continuous glucose monitoring: a consensus conference of the American Association of Clinical Endocrinologists and American College of Endocrinology. Endocr Pract. 2016;22(8):1008-1021. Battelino T, Danne T, Bergenstal RM, et al. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diabetes Care. 2019;42(8):1593-1603. Dexcom G6 Pro Unblinded Patient Guide. https://dexcompdf.s3-us-west-2.amazonaws.com/Dexcom-G6-Pro-Unblinded-Patient-Guide.pdf. Accessed October 12, 2020. Dexcom Announces FDA Clearance of New Dexcom G6 Pro CGM. https://provider.dexcom.com/industry-news/fda-authorizes-dexcom-g6-pro. Accessed October 2, 2020. Beck RW, Riddlesworth T, Ruedy K, et al. Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial. 2017;317(4):371-378. Beck RW, Riddlesworth TD, Ruedy K, et al. Continuous glucose monitoring versus usual care in patients with type 2 diabetes receiving multiple daily insulin injections: a randomized trial. Ann Intern Med. 2017;167(6):365-374. Polonsky WH, Hessler D, Ruedy KJ, Beck RW. The impact of continuous glucose monitoring on markers of quality of life in adults with type 1 diabetes: further findings from the DIAMOND randomized clinical trial. Diabetes Care. 2017;40(6):736-741. Pratley RE, Kanapka LG, Rickels MR, et al. Effect of continuous glucose monitoring on hypoglycemia in older adults with type 1 diabetes: a randomized clinical trial. 2020;323(23):2397-2406. Ruedy KJ, Parkin CG, Riddlesworth TD, Graham C. Continuous glucose monitoring in older adults with type 1 and type 2 diabetes using multiple daily injections of insulin: results from the DIAMOND trial. J Diabetes Sci Technol. 2017;11(6):1138-1146. Lind M, Polonsky W, Hirsch IB, et al. Continuous glucose monitoring vs conventional therapy for glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections: the GOLD randomized clinical trial. 2017;317(4):379-387. Frequently Asked Questions. https://provider.dexcom.com/products/dexcom-g6-pro/faqs. Accessed October 15, 2020. Dexcom Products: Dexcom G6 Pro. https://provider.dexcom.com/products/professional-cgm. Accessed October 15, 2020. How to Customize Alarm and Alerts. https://www.dexcom.com/faqs/how-to-customize-alarm-and-alerts. Accessed October 15, 2020. Trend Arrows and Treatment Decisions. https://s3-us-west-2.amazonaws.com/dexcompdf/HCP_Website/LBL015804+G6+Trend+Arrows+and+Treatment+Decisions.pdf. Accessed October 15, 2020. Why CGM? https://provider.dexcom.com/why-cgm. Accessed October 12, 2020. Pharmacy Coverage. https://provider.dexcom.com/pharmacy-coverage. Accessed October 12, 2020. Is There Reimbursement for Using Dexcom G6 Pro? https://provider.dexcom.com/faqs/there-reimbursement-using-dexcom-g6-pro. Accessed October 12, 2020. Hypoglycemia Unawareness. https://provider.dexcom.com/education-research/clinical-evidence/clinical-studies/real-time-continuous-glucose-monitoring-cgm. Accessed October 15, 2020. Garg SK, Wernicke-Panten K, Wardecki M, et al. Safety, immunogenicity, and glycemic control of insulin aspart biosimilar SAR341402 versus originator insulin aspart in people with diabetes also using insulin glargine: 12-month results from the GEMELLI 1 trial. Diabetes Technol Ther. 2020;22(7):516-526. Dexcom G6 Pro Blinded Patient Guide. https://dexcompdf.s3-us-west-2.amazonaws.com/HCP_Website/Dexcom+G6+Pro+Resources/LBL017177+Rev+004+Artwork%2C+Dexcom+G6+Pro+Blinded+Patient+Guide+US_r5_WEB.pdf. Accessed November 24, 2020. Dexcom CLARITY Diabetes Management Software. https://www.dexcom.com/clarity. Accessed May 15, 2020. Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized double-blind clinical trial comparing ultra rapid lispro with lispro in a basal-bolus regimen in patients with type 2 diabetes: PRONTO-T2D. Diabetes Care. Published online July 2, 2020. doi: 10.2337/dc19-2550. Klaff L, Cao D, Dellva MA, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. 2020;22(10):1799-1807. See omnystudio.com/listener for privacy information.

FDA 批准超速效赖脯胰岛素治疗糖尿病Diabetes Care 1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖Nature Review Cardiology SGLT2抑制剂：除血糖控制外的心血管益处机制Annals of Internal Medicine SGLT2抑制剂与糖尿病酮症酸中毒风险Cell ALK基因功能下调可以减肥超速效赖脯胰岛素（URLi）超速效赖脯胰岛素（URLi），在短效赖脯胰岛素的基础上改良的一种起效更快、持续时间更短的胰岛素，更大程度上模拟生理条件下、餐后胰岛素的释放曲线。超速效赖脯胰岛素与赖脯胰岛素相比，达到50%最大功效的时间分别为12.8分钟和25.4分钟，两者30分钟内的总暴露量分别为99.3pmol*h/L和34.8pmol*h/L。超速效赖脯胰岛素20分钟达到峰值，持续6小时。2020年6月，超速效赖脯胰岛素（LyumjevTM）已经被FDA批准上市。《PRONTO-T2D研究：超速效赖脯胰岛素与赖脯胰岛素在长效胰岛素基础上治疗2型糖尿病的3期临床研究》Diabetes Care，2020年6月 (1)评价赖脯胰岛素与超速效赖脯胰岛素（URLi）比较，在长效胰岛素基础上治疗2型糖尿病的疗效和安全性。共673位患者，在优化的、长效甘精胰岛素或长效德谷胰岛素的基础上，联合餐前赖脯胰岛素治疗8周后，患者随机分入餐前0-2分钟注射超速效赖脯胰岛素组、或普通赖脯胰岛素组。两种短效胰岛素均能改善患者糖化血红蛋白，治疗结束时糖化血红蛋白分别为6.92%和6.86%。在控制1小时和2小时餐后血糖的变化方面，超速效赖脯胰岛素优于赖脯胰岛素：餐后1小时两组差异为0.66 mmol/L，2小时两组差异为0.96 mmol/L。接受超速效赖脯胰岛素治疗的患者餐后30分钟至4.0小时内，餐后血糖偏移明显减少。两种治疗方法之间的总体治疗紧急不良事件，包括低血糖，发生率相似。结论：在2型糖尿病患者中，餐时注射的超速效赖脯胰岛素与餐前注射的赖脯胰岛素在控制糖化血红蛋白方面效果相当，但在餐后血糖控制方面优于赖脯胰岛素。《PRONTO-T1D研究：与赖脯胰岛素相比，超速效赖脯胰岛素改善了1型糖尿病患者餐后血糖控制》Diabetes Obesity Metabolism，2020年8月 (2)在一项为期26周的III期临床试验中，评估了超速效赖脯胰岛素（URLi）与赖脯胰岛素在成人1型糖尿病患者中的疗效和安全性。研究发现超速效赖脯胰岛素在控制糖化血红蛋白方面，不劣于赖脯胰岛素。餐时注射超速效赖脯胰岛素在减少餐时1小时和2小时餐后血糖方面明显更优秀：1小时两组血糖差异为1.55mmol/L， 2小时两组差异为1.73 mmol/L，餐后4小时低血糖发作降低37%（P = 0.013）。其他的不良反应发生率相似。结论：在1型糖尿病中，超速效赖脯胰岛素提供了良好的血糖控制，餐后血糖控制优于赖脯胰岛素。1型糖尿病的运动管理规律的运动对1型糖尿病儿童和青少年具有重要的健康和社交益处，应鼓励。有氧运动（步行、骑车）通常可降低血糖浓度，而无氧运动（全速跑、曲棍球、举重）通常会升高血糖，许多团体运动（足球、篮球、棒球）包含有氧和无氧运动。低血糖可能发生在运动期间或运动后不久，或者延迟至运动后数小时或睡眠时。高血糖可能发生在运动期间，或情绪激动时。建议运动前、运动30分钟、运动恢复期和睡前监测血糖。《1型糖尿病运动后血糖控制与残留的β细胞功能有关》Diabetes Care，2020年10月 (3)研究旨在评价剩余β细胞功能对1型糖尿病患者运动后血糖的影响。研究招募30名、1型糖尿病病史≥3年的参与者，首先盲法进行7天的自由生活数据采集；然后进行3小时混合餐试验评估C肽和胰高血糖素水平。使用C肽峰值将参与者分成极低C肽组（C肽浓度200 pmol/L）；最后，参与者完成45分钟在60%VO2峰值的运动，然后再进行48小时的连续血糖检测。在运动后12小时和24小时，高C肽组参与者中葡萄糖正常的时间显著高于其他两组的参与者（高C肽组：12小时 73.5%，24 h 76.3%；低C肽组：12小时43.6%，24小时52.3%；极低C肽组12小时40.6%，24小时 51.3%）。而且，高C肽组参与者中高血糖的时间显著低于其他两组，血糖的波动也更小（P < 0.01）。从运动前到运动后24小时连续血糖检测的结果发现：高C肽组的参与者血糖控制得更好了（正常血糖的时间增加了12.1%），但另外两组的血糖控制得更差了（正常血糖的时间减少了9.1%和16.2%）。结论：剩余的β细胞功能可能部分解释了1型糖尿病患者运动后血糖的个体间差异，量化C肽有助于为患者提供个性化、针对性的运动支持。《1型糖尿病与有氧运动：在长效基础胰岛素基础上，运动前单次口服果糖可降低运动性低血糖的风险》Diabetes Care，2020年8月 (4)虽然调整胰岛素是降低1型糖尿病患者运动相关性低血糖风险的既定策略，但对超长效基础胰岛素治疗的患者来说，这并不容易实现。目前的研究确定了1型糖尿病患者在运动前摄入果糖是否能降低因运动引起的低血糖的风险。研究中14名参与分别完成了两次60min的有氧自行车运动，一次在运动前30min服用20g果糖，一次不服用果糖。摄入果糖的情况下，患者60min平均只发生1次低血糖事件，而对照组在运动的约30分钟内发生6次低血糖事件，果糖将运动时低血糖的风险降低了87.8%。服用果糖的运动期间平均血糖为7.3mmol/L，对照组为5.5mmol/L。摄取果糖后30分钟内休息时，患者的乳酸水平较高，但运动期间即回到基线。结论：对于使用超长效胰岛素的1型糖尿病患者而言，运动前摄取果糖是一种简单可行、有效且耐受良好的策略，可以减轻运动引起的低血糖风险，同时避免高血糖。《1型糖尿病业余运动员：9天中高强度自行车训练意外的升高血糖》Diabetes Care，2020年8月 (5)1型糖尿病中，心率变异性（HRV）降低可能是早期的自主神经功能障碍的一种表现；1型糖尿病患者，尤其是剧烈运动和长时间运动时，血糖会急剧变化，从而对心率变异性产生负面影响。本研究中，20名患有1型糖尿病的业余运动员9天骑行1500公里。研究出乎意料的发现，骑行的距离越长，高血糖时间越长，低血糖时间越短，同时夜间心率变异性越低；这可能和副交感神经张力降低有关。而且在这一过程中，胰岛素的使用没有改变，从饮食中摄入的碳水化合物也没有变化减少。结论：在患有1型糖尿病的运动爱好者中，长时间中高强度运动加重了高血糖，而高血糖与副交感神经及心脏功能相关；考虑潜在的对心脏的有害后果，未来的工作应该集中在理解和管理运动引起的高血糖现象。《1型糖尿病与中高强度运动：在运动前，采用长效胰岛素和胰岛素泵混合方案》Lancet Diabetes & Endocrinology，2020年6月 (6)使用持续皮下注射胰岛素泵（CSII）的1型糖尿病患者通常会在长时间运动前移除泵，但这种方法可能会增加高血糖和酮症的风险。该研究目的是评估一种混合方法的有效性和安全性，即通过胰岛素泵混合德谷胰岛素qd（一种长效胰岛素）提供每日必须的基础胰岛素治疗。这是一个单中心、开放标签、概念验证、随机交叉试验中，招募了平时规律使用胰岛素泵的1型糖尿病患者，开放标签分入单用胰岛素泵组和胰岛素泵联合长效胰岛素治疗组中，两组患者均在运动前60分钟停止胰岛素泵，运动后立即重新连接。与通常的胰岛素泵方案相比，混合胰岛素泵方案的参与者在中高强度运动后6小时内，血糖稳定（4-10mmol/L）的时间显著延长；在家运动时的高血糖持续时间更短。两种干预措施低血糖时间和低血糖事件方面没有显著差异。结论：清晨注射一次长效胰岛素和胰岛素泵的混合方案似乎对有规律运动习惯的1型糖尿病成人更加安全有效的。小羽点评：1型糖尿病病患者的残余β细胞功能和自主神经功能障碍均会影响患者运动后的血糖。β细胞残余功能越差，血糖波动越大；长时间中高强度的运动，副交感神经张力降低，引发高血糖。为了更高的减少运动后高血糖，可以采用长效胰岛素和胰岛素泵混合方案；为了减少运动相关低血糖时间，可以在运动前服用果糖。2型糖尿病的药物治疗-SGLT2抑制剂钠-葡萄糖协同转运蛋白2（SGLT2）表达于肾近端小管，介导约90%的滤过葡萄糖的重吸收。SGLT2抑制剂促进肾脏对葡萄糖的排泄，因此可降低血糖、降低血压和体重，通常不会导致低血糖。SGLT2最常见的副作用为外阴阴道假丝酵母菌感染及低血压。对于合并糖尿病肾病、心力衰竭和冠心病的患者，可考虑优先使用。在《内分泌科星期五 Episode 5》中，我们聊到了SGLT2抑制剂在1型糖尿病患者中的应用，不知道各位听众是否还记得。由于SGLT2抑制剂有增加1型糖尿病患者酮症酸中毒的风险，因此欧洲仅批准了SGTL2抑制剂用于BMI>27kg/m2的1型糖尿病患者。《队列研究：SGLT2抑制剂与糖尿病酮症酸中毒风险》Annals of Internal Medicine，2020年9月 (7)研究旨在评估SGLT-2抑制剂与DPP-4抑制剂相比，是否增加2型糖尿病患者酮症酸中毒的风险。研究纳入20757名新使用SGLT-2抑制剂的患者和20757名新使用DPP-4抑制剂的患者。在370 454人年的随访中，共发生了521例酮症酸中毒。与DPP-4抑制剂相比，SGLT-2抑制剂与酮症酸中毒风险增加相关。其中，达格列净的风险比为1.86；恩格列净的风险比为2.52；卡格列净的风险比3.58。这种关联性与年龄和性别无关，在曾接受过胰岛素治疗的人群中，这种风险风险似乎更低。结论：SGLT-2抑制剂使用后酮症酸中毒风险增加近3倍，不同药物的风险比略有不同。《SGLT2抑制剂：除血糖控制外的心血管益处机制》Nature Review Cardiology，2020年7月(8)SGLT2抑制剂除了控制血糖，也可以改善心血管和肾脏结局，且获益扩展到有射血分数降低的心功能不全的非糖尿病患者中。其中的机制可能包括：（1）早期尿钠与血浆体积减少、随之而来的血细胞比积升高、血管功能改善、血压降低和组织钠的变化都可能发挥作用；（2）减少脂肪组织介导的炎症反应和炎性细胞因子的生产，心脏和肾脏转向酮体代谢，减少氧化应激，降低尿酸，减少肾小球渗透压和蛋白尿，抑制晚期糖基化产物生成。《EMPEROR-Reduce研究：恩格列净治疗心衰患者的心血管和肾脏结局》New England Journal of Medicine，2020年8月 (9)这项双盲试验中，随机分配3730名II、III或IV型心衰、射血分数≤40%的患者，除推荐治疗外，随机接受恩格列净10mg qd或安慰剂治疗。随访16个月，恩格列净组和安慰剂组中，主要终点事件（心血管死亡和心衰住院）的发生率分别为19.4%和24.7%（风险比0.75，P < 0.001）。无论是否患有糖尿病，结果是一致的。两组中肾小球滤过率下降的幅度分别为-0.55ml/min和-2.28ml/min（P < 0.001）。应用恩格列净无并发症的生殖道感染发生率更高。结论：无论是否合并糖尿病，射血分数≤40%的心力衰竭患者加用恩格列净可以降低心血管死亡或心衰住院的风险。《DECLARE-TIMI 58研究的探索性分析：达格列净与2型糖尿病患者的心脏、肾脏和四肢的预后的关系》Circulation，2020年8月 (10)有研究显示SGLT2抑制剂增加2型糖尿病的截肢的风险。在这项探索性分析中，纳入了DECLARE-TIMI 58研究中的、17 160例2型糖尿病患者，6%患有外周动脉疾病PAD。主要疗效结果为MACE(心血管[CV]死亡、心肌梗死、卒中)、CV死亡/HHF和肾脏疾病进展。截肢、外周血管重建和肢体缺血不良事件由盲的审稿人进行现场报道和分类。患有外周动脉疾病的患者，死亡、心肌梗死、卒中（风险比1.23）、心血管死亡、心衰住院（风险比1.60）、肾脏疾病进展（风险比1.60）和截肢（风险比8.37）的风险显著升高。无论是否患有外周动脉疾病，服用达格列净后，心血管死亡、心衰在入院的相对风险均降低（风险比 0.86和0.82，p=0.79），肾脏疾病进展相对风险也降低（风险比0.78和0.76，P=0.84）。随访过程中，共记录到了560例患者的肢体缺血事件、和407例截肢事件。总体而言，使用达格列净与安慰剂相比，肢体缺血不良事件和截肢的风险没有统计学差异（风险比1.07和1.09）。结论：有外周动脉疾病的患者发生心血管死亡、心衰入院和肾脏结局的风险更高，使用达格列净能够获益；但与肢体缺血不良事件没有显著相关性。《VERTIS CV研究：埃格列净对2型糖尿病、冠心病患者的心血管事件结局的影响》New England Journal of Medicine，2020年9月 (11)这项多中心、双盲试验中，随机将8246名患有2型糖尿病和冠心病的患者，分配至埃格列净5mg qd、埃格列净15mg qd或安慰剂组。平均随访3年半，埃格列净组和安慰剂组均有11.9%的患者出现了不良心血管事件。埃格列净组和安慰剂组，分别有8.1%和9.1%的参与者死于心血管疾病或因心衰恶化住院（P=0.11），肾脏原因死亡、肾脏替代治疗或肌酐水平上升2倍的发生率也没有统计学差异。结论：在患有2型糖尿病和动脉粥样硬化性心血管疾病的患者中，埃格列净在主要不良心血管事件方面并不逊于安慰剂。胖基因《基础研究：在瘦的人群中定义ALK基因》Cell，2020年6月 (12)为研究肥胖的遗传易感性，但我们对健康的瘦的人群（BMI值最低的6个百分位数）进行了全基因组关联分析研究（GWAS），发现间变性淋巴瘤激酶（ALK）是一个候选的“瘦”基因。下丘脑神经元中的表达的ALK，通过交感神经对脂肪组织分解作用的影响，来控制能量的消耗。ALK突变可以增强机体的分解代谢能力，从而有效抵抗体重增加。在果蝇中，RNAi介导的ALK基因敲除，可以降低甘油三酯水平。在小鼠中，ALK基因缺失导致瘦的动物对饮食诱导的肥胖、和瘦素突变诱导的肥胖，均具有显著的抵抗能力。结论：这项遗传和机制实验确定ALK是一个胖基因，参与抵抗体重增加。小羽点评：ALK抑制剂已经用于癌症的治疗了。如果在可以关闭ALK或使ALK基因功能下调，那么是否能够帮助我们保持苗条，甚至减重呢？参考文献1.Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D. Diabetes Care. 2020.2.Klaff L, Cao D, Dellva MA, Tobian J, Miura J, Dahl D, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. 2020.3.Taylor GS, Smith K, Capper TE, Scragg JH, Bashir A, Flatt A, et al. Postexercise Glycemic Control in Type 1 Diabetes Is Associated With Residual β-Cell Function. Diabetes Care. 2020;43(10):2362-70.4.Kosinski C, Herzig D, Laesser CI, Nakas CT, Melmer A, Vogt A, et al. A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study. Diabetes Care. 2020.5.Lespagnol E, Bocock O, Heyman J, Gamelin FX, Berthoin S, Pereira B, et al. In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in a State of Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability. Diabetes Care. 2020.6.Aronson R, Li A, Brown RE, McGaugh S, Riddell MC. Flexible insulin therapy with a hybrid regimen of insulin degludec and continuous subcutaneous insulin infusion with pump suspension before exercise in physically active adults with type 1 diabetes (FIT Untethered): a single-centre, open-label, proof-of-concept, randomised crossover trial. Lancet Diabetes Endocrinol. 2020;8(6):511-23.7.Douros A, Lix LM, Fralick M, Dell'Aniello S, Shah BR, Ronksley PE, et al. Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Ann Intern Med. 2020;173(6):417-25.8.Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020.9.Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. New England Journal of Medicine. 2020;383(15):1413-24.10.Bonaca MP, Wiviott SD, Zelniker TA, Mosenzon O, Bhatt DL, Leiter LA, et al. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58. Circulation. 2020;142(8):734-47.11.Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-35.12.Orthofer M, Valsesia A, Magi R, Wang QP, Kaczanowska J, Kozieradzki I, et al. Identification of ALK in Thinness. Cell. 2020;181(6):1246-62 e22.

FDA 塞帕替尼治疗RET基因突变的甲状腺癌的新药JAMA 成人减肥手术的好处和风险Science Advance 可测定皮质醇的隐形眼镜塞帕替尼（selpercatinib）第22期，呼吸科星期二介绍了RET选择性抑制剂塞帕替尼（selpercatinib）被批准用于治疗RET融合阳性非小细胞肺癌的最新研究。甲状腺髓样癌中，约有70%存在RET突变，2020年5月，塞帕替尼（selpercatinib）同时被FDA批准用于治疗RET驱动的甲状腺癌。《LIBRETTO-001研究：塞帕替尼对RET驱动的甲状腺癌的疗效的1/2期临床研究》New England Journal of Medicine，2020年8月 (1)研究纳入了RET突变型甲状腺髓性癌患者，接受塞帕替尼治疗，其中一部分患者曾接受过凡德他尼（vandetanib）或卡博替尼（cabozantinib）治疗的。在RET突变型甲状腺髓样癌患者中，曾接受凡德他尼和/或卡博替尼治疗的55名参与者中，缓解率为69%，1年无进展率为82%。未接受过凡德他尼和/或卡博替尼治疗的88名参与者中，缓解率73%，1年无进展率为92%。最常见的严重不良事件是高血压、转氨酶升高、低钠血症和腹泻。结论：在RET基因突变的甲状腺癌髓性患者中，塞帕替尼表现出持久的疗效。肥胖肥胖是一种疾病，会显著增加死亡率和诸多健康风险，包括2型糖尿病、高血压、血脂异常和冠心病，肥胖者应减重。25kg/m2≤BMI

FDA 塞帕替尼治疗RET基因突变的甲状腺癌的新药JAMA 成人减肥手术的好处和风险Science Advance 可测定皮质醇的隐形眼镜塞帕替尼（selpercatinib）第22期，呼吸科星期二介绍了RET选择性抑制剂塞帕替尼（selpercatinib）被批准用于治疗RET融合阳性非小细胞肺癌的最新研究。甲状腺髓样癌中，约有70%存在RET突变，2020年5月，塞帕替尼（selpercatinib）同时被FDA批准用于治疗RET驱动的甲状腺癌。《LIBRETTO-001研究：塞帕替尼对RET驱动的甲状腺癌的疗效的1/2期临床研究》New England Journal of Medicine，2020年8月 (1)研究纳入了RET突变型甲状腺髓性癌患者，接受塞帕替尼治疗，其中一部分患者曾接受过凡德他尼（vandetanib）或卡博替尼（cabozantinib）治疗的。在RET突变型甲状腺髓样癌患者中，曾接受凡德他尼和/或卡博替尼治疗的55名参与者中，缓解率为69%，1年无进展率为82%。未接受过凡德他尼和/或卡博替尼治疗的88名参与者中，缓解率73%，1年无进展率为92%。最常见的严重不良事件是高血压、转氨酶升高、低钠血症和腹泻。结论：在RET基因突变的甲状腺癌髓性患者中，塞帕替尼表现出持久的疗效。肥胖肥胖是一种疾病，会显著增加死亡率和诸多健康风险，包括2型糖尿病、高血压、血脂异常和冠心病，肥胖者应减重。25kg/m2≤BMI

FDA 首次批准治疗Grave's眼病的新药JAMA 连续发表3篇文章讨论连续血糖监测在1型糖尿病患者中的意义Lancet子刊 胰岛素在中枢神经系统中能控制代谢和食物摄取替妥木单抗（teprotumumab）替妥木单抗（teprotumumab）是胰岛素样生长因子Ⅰ受体（IGF-ⅠR）的单克隆抗体，2019年11月，FDA批准替妥木单抗用于治疗活动性Grave's眼病，这是第一个获批治疗此病症的药物。《OPTIC研究：替妥木单抗治疗活动性Grave's眼病的3期临床研究》New England Journal of Medicine，2020年1月 (1)该研究旨在评估替妥木单抗对活动性Grave's眼病的安全性和有效性。这项随机、双盲、安慰剂对照、3期多中心试验中，共招募83名活动性Grave's眼病的患者，随机分为干预组（替妥木单抗 首剂为10mg/kg，之后为20 mg/kg，每3周一次）或安慰剂组，治疗共持续21周。24周后，干预组和安慰剂组中，眼球突出减少≥2mm的比例分别为38%和10%，总体缓解率分别为78%和7%；临床活动度评分0-1分的比例分别为59%和21%；复视症状缓解的比例分别为68%和29%。影像学检查的替妥木单抗组的6例患者中，观察到眼外肌缩小、或眼眶脂肪量减少。结论：21周的替妥木单抗治疗相比安慰剂，可以显著改善Grave's患者突眼症状、临床活动度评分、复视。1型糖尿病的连续血糖检测1型糖尿病患者中，血糖控制的目标是糖化血红蛋白

FDA 首次批准治疗Grave's眼病的新药JAMA 连续发表3篇文章讨论连续血糖监测在1型糖尿病患者中的意义Lancet子刊 胰岛素在中枢神经系统中能控制代谢和食物摄取替妥木单抗（teprotumumab）替妥木单抗（teprotumumab）是胰岛素样生长因子Ⅰ受体（IGF-ⅠR）的单克隆抗体，2019年11月，FDA批准替妥木单抗用于治疗活动性Grave's眼病，这是第一个获批治疗此病症的药物。《OPTIC研究：替妥木单抗治疗活动性Grave's眼病的3期临床研究》New England Journal of Medicine，2020年1月 (1)该研究旨在评估替妥木单抗对活动性Grave's眼病的安全性和有效性。这项随机、双盲、安慰剂对照、3期多中心试验中，共招募83名活动性Grave's眼病的患者，随机分为干预组（替妥木单抗 首剂为10mg/kg，之后为20 mg/kg，每3周一次）或安慰剂组，治疗共持续21周。24周后，干预组和安慰剂组中，眼球突出减少≥2mm的比例分别为38%和10%，总体缓解率分别为78%和7%；临床活动度评分0-1分的比例分别为59%和21%；复视症状缓解的比例分别为68%和29%。影像学检查的替妥木单抗组的6例患者中，观察到眼外肌缩小、或眼眶脂肪量减少。结论：21周的替妥木单抗治疗相比安慰剂，可以显著改善Grave's患者突眼症状、临床活动度评分、复视。1型糖尿病的连续血糖检测1型糖尿病患者中，血糖控制的目标是糖化血红蛋白

International guidelines recommend patient self-directed titration of insulin where initiating a basal regimen. However, these same guidelines do not appear to provide any clear direction of which algorithm should be used, other than it be “evidence-based”. With this in mind, how should we select between algorithms to offer our patients? Join us for a quick summary of three example algorithms before discussing optimal approaches with Dr Ronald Goldenberg from LMC Diabetes & Endocrinology in Thornhill, Canada. References: Davies MJ,e t al. Diabetes Care. 2018; 41(12): 2669-2701 ADA. Diabetes Care 2020; 43(Suppl 1): S1-S2 Davies M, et al. Diabetes Care. 2005; 28(6):1282-1288 Meneghini L, et al. Diabetes Obes Metab. 2007; 9(6):902-13 Yale JF, et al. Poster presented at: ATTD 2017, 15-18 February, Paris France. This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education.

A mountain of data exist for each antihyperglycaemic agent, from metformin through to the most recently approved agent. Considering all these data, what are the most significant observations to date? Join Professor Jens Juul Holst from the University of Copenhagen for a summary of data on DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists, including a particular focus on within-class differences and whether oral vs injectable formulations have different effects References - Pinto LC, et al. Diabetol Metab Syndr. 2015; 7(Suppl 1): A58 - Craddy P, et al. Diabetes Ther. 2014;5(1):1-41. - Uccellatore A, et al. Diabetes Ther. 2015;6(3):239-56 - Nauck MA, et al. Diabetologia. 2016; 59(2):266-74. - Aroda VR, et al. Diabetes Obes Metab. 2020; 22(3):303-314 - Ahrén B. Front Endocrinol (Lausanne). 2019;10:376 - Rosenstock J, et al. JAMA. 2019 Sep 19. [Epub ahead of print] - Kristensen SL. Lancet Diabetes Endocrinol. 2019; 7(10):776-785 - Romera I, et al. Diabetes Therapy 2019; 10:5-19 - McMurray JJV, et al. N Engl J Med 2019; 381:1995-2008 - Perkovic V, et al. N Engl J Med 2019; 380:2295-2306 - Fitchett D, et al. Diabetes Obes Metab. 2019;21 Suppl 2:34-42. This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education.

בפרק הזה נעבור על המיתוסים הנפוצים ביותר בתזונה קטוגנית. (כולל לינקים למחקרים שהסתמכתי עליהם למטה) המיתוסים שנבדוק: * האם תזונה דלת פחמימות ותזונה קטוגנית זה אותו דבר * האם התזונה הטובה ביותר לאנושות היא תזונה מאוד דלת פחמימות או קטוגנית * האם האינסולין חשוב מהקלוריות, והקלוריות לא חשובות * האם חייבים לאכול בשר ושומן מהחי בתזונה קטוגנית * האם תזונה קטוגנית פוגעת בכליות הורידו את פרק החינם מהקורס אכילה לסירוגין לבריאות והרזיה או עברו לקורס המלא אכילה לסירוגין הורידו את פרק החינם מהקורס לרזות בשפת הגוף או עברו לקורס המלא לרזות בשפת הגוף להרצאה מלאה ופרקטית על אכילה רגשית הצטרפו לקבוצת דלי פחמימות ישראל בפייסבוק הצטרפו לקבוצת צום לסירוגין בפייסבוק ====== רפרנסים: https://link.springer.com/article/10.1007/s11154-019-09518-8?fbclid=IwAR1eXwSJmSXYwaR7g3UTvrKnfdDU5tUqZBa7n4NbqQQCMjSZzQKT03XmJ5c Nina Mohorko et al. Weight loss, improved physical performance, cognitive function, eating behavior and metabolic profile in a 12-week ketogenic diet in obese adults. Nutr Res 2019;62:64-67 KJ Martin-McGill et al. Ketogenic diets for drug‐resistant epilepsy. Chocrane Database of systematic reviews 2018. Paoli A et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013; 67: 789–796. Feinman RD et al. Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 2015;31:1-13 Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 2004;25:311–314 Vanitallie TB et ak. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 2005;64:728 –730 Hallberg SJ et al. Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study Diabetes. Diabetes Ther:2018;9:583. Tay J et al. Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial. Diabetes Obes Metab. 2018 Apr;20(4):858-871. https://onlinelibrary.wiley.com/doi/abs/10.1111/obr.12230 https://www.atid-eatright.org.il/prdFiles/%D7%A0%D7%99%D7%99%D7%A8%20%D7%A2%D7%9E%D7%93%D7%94%20%D7%9B%D7%91%D7%93%20%D7%A9%D7%95%D7%9E%D7%A0%D7%99%202018.pdf https://www.atid-eatright.org.il/prdFiles/%D7%91%D7%A8%D7%99%D7%90%D7%98%D7%A8%D7%99%D7%94.pdf https://www.sciencedirect.com/science/article/abs/pii/S0026049514002418 https://www.sciencedirect.com/science/article/abs/pii/S1043276015001356 https://www.jci.org/articles/view/78362 https://www.sciencedirect.com/science/article/pii/S1550413115004830 https://www.sciencedirect.com/science/article/pii/S1550413117302851 https://www.sciencedirect.com/science/article/pii/B9780124114623000461 https://www.sciencedirect.com/science/article/abs/pii/S1548559515000592 https://www.mdpi.com/2072-6643/11/1/196 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206134

Episode 282 brings you the COMPLETE guide on metformin! Every possible interaction, MoA, and question has been answered and summarized here on this episode! My goal for this is to truly summarize the full picture of metformin as too many people demonize it for reasons that literally are so insignificant, they should barely even be paid a notice. So with that in mind, get your notepads ready, this one is FULL of information! And yes, a few references for those of you that wish to read further!   REFERENCES 1. Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221–228. [PubMed] 2. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One. 2013;8(8):e71583. [PMC free article] [PubMed] 3. Cohen RD, Woods HF. Clinical and biochemical aspects of lactic acidosis. Philadelphia: Blackwell Scientific Publications; 1976. 4. Metformin hydrochoride. Boxed warning. [October 6, 2015]. Available at: https://dailymed​.nlm​.nih.gov/dailymed/fda/fdaDrugXsl​.cfm?setid​=b8004451-7b26-425b-b5ea-cbb1b08e30e3&type=display. 5. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668–2675. [PMC free article] [PubMed] 6. Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med. 1992;152(11):2333–2336. [PubMed] 7. Goergen SK, Rumbold G, Compton G, Harris C. Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology. 2010;254(1):261–269. [PubMed] 8. Kajbaf F, Arnouts P, de Broe M, Lalau JD. Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world. Pharmacoepidemiol Drug Saf. 2013;22(10):1027–1035.[PubMed] 9. Calabrese AT, Coley KC, DaPos SV, Swanson D, Rao RH. Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy. Arch Intern Med. 2002;162(4):434–437. [PubMed] 10. Emslie-Smith AM, Boyle DI, Evans JM, Sullivan F, Morris AD. Contraindications to metformin therapy in patients with Type 2 diabetes--a population-based study of adherence to prescribing guidelines. Diabet Med. 2001;18(6):483–488. [PubMed] 11. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. [June 16, 2016]. Available at: http://www​.fda.gov/Drugs​/DrugSafety/ucm493244.htm. 12. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med. 2006;354(23):2473–2483. [PubMed] 13. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabtologia. 2015;58(3):429–442. [PubMed] 14. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012;60(5):850–886. [PubMed] 15. Flory JH, Hennessy S. Metformin use reduction in mild to moderate renal impairment: possible inappropriate curbing of use based on food and drug administration contraindications. JAMA Intern Med. 2015;175(3):458–459. [PubMed] 16. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010;(4) CD002967. [PubMed] 17. Organization for Economic Cooperation and Development. [October 20, 2015]. Available at: http://www​.oecd.org/about​/membersandpartners​/list-oecd-member-countries.htm. 18. Eurich DT, Weir DL, Majumdar SR, et al. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail. 2013;6(3):395–402. [PubMed] 19. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–470. [PubMed] 20. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612. [PMC free article] [PubMed] 21. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [PMC free article] [PubMed] 22. Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality; [October 6, 2015]. Available at: http://www​.effectivehealthcare​.ahrq.gov/index​.cfm/search-for-guides-reviews-and-reports​/?pageaction=displayproduct&productid=318. 23. Santaguida PL, Raina P, Ismaila P. The Development of the McHarm Quality Assessment Scale for adverse events. 2012 24. Viswanathan M, Ansari M, Berkman N. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville (MD): Agency for Healthcare Research and Quality (US); Mar 8, 2012. [October 6, 2015]. Assessing the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions. [Internet] 2008-. Available from: http://www​.ncbi.nlm.nih​.gov/books/NBK91433/ 25. Andersson C, Olesen JB, Hansen PR, et al. Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study. Diabetologia. 2010;53(12):2546–2553. [PubMed] 26. Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28(10):2345–2351. [PubMed] 27. Weir DL, McAlister FA, Senthilselvan A, Minhas-Sandhu JK, Eurich DT. Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study. JACC Heart Fail. 2014;2(6):573–582. [PubMed] 28. Wang Z. Converting odds ratio to relative risk in cohort studies with partial data information. Journal of Statistical Software. 2013;55(5):1–11. 29. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta-analyses. JAMA. 2014;312(6):623–630. [PubMed] 30. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. [PubMed] 31. Knapp G, Hartung J. Improved tests for a random effects meta-regression with a single covariate. Stat Med. 2003;22(17):2693–2710. [PubMed] 32. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–406. [PubMed] 33. Richy FF, Sabido-Espin M, Guedes S, Corvino FA, Gottwald-Hostalek U. Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care. 2014;37(8):2291–2295. [PubMed] 34. Eppenga WL, Lalmohamed A, Geerts AF, et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care. 2014;37(8):2218–2224. [PubMed] 35. Romero SP, Andrey JL, Garcia-Egido A, et al. Metformin therapy and prognosis of patients with heart failure and new-onset diabetes mellitus. A propensity-matched study in the community. Int J Cardiol. 2013;166(2):404–412. [PubMed] 36. Ito H, Ohno Y, Yamauchi T, Kawabata Y, Ikegami H. Efficacy and safety of metformin for treatment of type 2 diabetes in elderly Japanese patients. Geriatr Gerontol Int. 2011;11(1):55–62. [PubMed] 37. Sterner G, Elmståhl S, Frid A, et al. Renal function in a large cohort of metformin treated patients with type 2 diabetes mellitus. British Journal of Diabetes and Vascular Disease. 2012;12(5):227–231. 38. Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014;60(6):2008–2016. [PMC free article] [PubMed] 39. Becquemont L, Bauduceau B, Benattar-Zibi L, et al. Cardiovascular Drugs and Metformin Drug Dosage According to Renal Function in Non-Institutionalized Elderly Patients. Basic Clin Pharmacol Toxicol. 2015[PubMed] 40. Ekström N, Schiöler L, Svensson AM, et al. Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: A cohort study from the Swedish National Diabetes Register. BMJ Open. 2012;2:4. Article Number: e001076. [PMC free article] [PubMed] 41. Aguilar D, Chan W, Bozkurt B, Ramasubbu K, Deswal A. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circulation: Heart Failure. 2011;4(1):53–58. [PMC free article] [PubMed] 42. Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005;111(5):583–590. [PubMed] 43. Morgan CL, Mukherjee J, Jenkins-Jones S, Holden SE, Currie CJ. Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study. Diabetes Obes Metab. 2014;16(10):957–962. [PubMed] 44. Roussel R, Travert F, Pasquet B, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010;170(21):1892–1899. [PubMed] 45. Evans JM, Doney AS, AlZadjali MA, et al. Effect of Metformin on mortality in patients with heart failure and type 2 diabetes mellitus. Am J Cardiol. 2010;106(7):1006–1010. [PubMed] 46. Inzucchi SE, Masoudi FA, Wang Y, et al. Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial infarction: insights from the National Heart Care Project. Diabetes Care. 2005;28(7):1680–1689. [PubMed] 47. Shah DD, Fonarow GC, Horwich TB. Metformin therapy and outcomes in patients with advanced systolic heart failure and diabetes. J Card Fail. 2010;16(3):200–206. [PMC free article] [PubMed] 48. Tinetti ME, McAvay G, Trentalange M, Cohen AB, Allore HG. Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study. BMJ. 2015;351:h4984. [PMC free article] [PubMed] 49. Ampuero J, Ranchal I, Nunez D, et al. Metformin inhibits glutaminase activity and protects against hepatic encephalopathy. PloS One. 2012;7(11):e49279. [PMC free article] [PubMed] 50. Nkontchou G, Cosson E, Aout M, et al. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab. 2011;96(8):2601–2608. [PubMed] 51. Blonde L, Rosenstock J, Mooradian AD, Piper BA, Henry D. Glyburide/metformin combination product is safe and efficacious in patients with type 2 diabetes failing sulphonylurea therapy. Diabetes Obes Metab. 2002;4(6):368–375. [PubMed] 52. Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care. 2005;28(3):539–543. [PubMed] 53. Garber AJ, Larsen J, Schneider SH, Piper BA, Henry D. Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes. Diabetes Obes Metab. 2002;4(3):201–208. [PubMed] 54. Gregorio F, Ambrosi F, Manfrini S, et al. Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin. Diabet Med. 1999;16(12):1016–1024. [PubMed] 55. Hanefeld M, Brunetti P, Schernthaner GH, Matthews DR, Charbonnel BH. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care. 2004;27(1):141–147. [PubMed] 56. Marre M, Howlett H, Lehert P, Allavoine T. Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin. Diabet Med. 2002;19(8):673–680. [PubMed] 57. Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Obes Metab. 2009;11(8):804–812.[PubMed] 58. Bannister CA, Holden SE, Jenkins-Jones S, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014;16(11):1165–1173. [PubMed] 59. Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care. 2008;31(11):2086–2091. [PMC free article] [PubMed] 60. Huizinga MM, Roumie CL, Greevy RA, et al. Glycemic and weight changes after persistent use of incident oral diabetes therapy: a Veterans Administration retrospective cohort study. Pharmacoepidemiol Drug Saf. 2010;19(11):1108–1112. [PubMed] 61. Leung S, Mattman A, Snyder F, Kassam R, Meneilly G, Nexo E. Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem. 2010;43(9):759–760. [PubMed] 62. Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157(9):601–610. [PMC free article] [PubMed] 63. Wang CP, Lorenzo C, Espinoza SE. Frailty Attenuates the Impact of Metformin on Reducing Mortality in Older Adults with Type 2 Diabetes. J Endocrinol Diabetes Obes. 2014;2(2) [PMC free article] [PubMed] 64. Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b4731. [PMC free article] [PubMed] 65. American Diabetes Association. Standards of Medical Care in Diabetes--2016. [June 30, 2016]. Available at: http://care​.diabetesjournals​.org/content/39/Supplement_1. 66. Bolen S, Tseng E, Hutfless S, et al. Diabetes Medications for Adults With Type 2 Diabetes: An Update.Rockville (MD): Agency for Healthcare Research and Quality (US); 2016. AHRQ Comparative Effectiveness Reviews. 67. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–149. [PubMed] 68. Tuot DS, Lin F, Shlipak MG, et al. Potential impact of prescribing metformin according to eGFR rather than serum creatinine. Diabetes Care. 2015;38(11):2059–2067. [PMC free article] [PubMed] 69. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. Jama. 2016;316(3):313–324. [PubMed] 70. MacDonald MR, Eurich DT, Majumdar SR, et al. Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database. Diabetes Care. 2010;33(6):1213–1218. [PMC free article] [PubMed] 71. U.S. Department of Veterans Affairs. Office of Research & Development. VA CSP Study No. 597: Diuretic Comparison Project. [August 29, 2016]. Available at: http://www​.research.va​.gov/programs/csp/597/ 72. Canadian Diabetes Association. Clinical Practice Guidelines: Pharmacotherapy for Type 2 Diabetes. [June 30, 2016]. Available at: http://guidelines​.diabetes​.ca/bloodglucoselowering​/pharmacologyt2-(1) 73. Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012;22(11):820–827. [PMC free article] [PubMed] 74. Weir MA, Gomes T, Mamdani M, et al. Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study. Nephrol Dial Transplant. 2011;26(6):1888–1894. [PubMed]      •••SUPPORT OUR SPONSORS•••   (COACHING) Alex - www.theprepcoach.com   (FREE OPEN FORUM w/ EXCLUSIVE VIDEOS) http://www.theprepcoachforum.com   (SUPPLEMENTS) www.projectad.me___use discount code “BFR25” to save off your order!   (RESEARCH CHEMS) www.maresearchchems.net___use discount code “alex15” to save off your order!   (SPECIALTY SUPPS) www.masupps.com___use discount code “alex20” to save off your order!   (INJECTABLE L-CARNITINE) www.synthetek.com___use discount code “alexkikel” to save off your order!   (BULK SUPPLEMENTS) www.truenutrition.com___use discount code “AXK5” to save off your order!       •••FIND THE EPISODES•••   ITUNES:https://itunes.apple.com/us/podcast/beastfitness-radios-podcast/id1065532968   LIBSYN:http://beastfitnessradio.libsyn.com   VIMEO: www.vimeo.com/theprepcoach        •••PREP COACH APPAREL•••   https://teespring.com/stores/the-prep-coach-apparel    

Ref: When basal insulin is not enough: A dose-response relationship between insulin glargine 100 units/mL and glycaemic control. Diabetes Obes Metab. 2019 Jun;21(6):1305-1310.

Lipid-lowering medication is associated with decreased risk of diabetic retinopathy and the need for treatment in patients with type 2 diabetes: A real-world observational analysis of a health claims database. Diabetes Obes Metab. 2018 Oct;20(10):2351-2360.

However you choose to move your body -, whether it’s a daily run, yoga, team competition or a Spartan Ultra - once you’re done, it’s time to recover. What does the body need to heal and regenerate? We’ll review some key nutrients and foods that can restore and replenish so you’re ready for whatever comes next. WHAT WE COVER:   Movement or exercise for the body is one of the pillars of long-term health and wellness. But, once you’ve pushed your body hard it’s time to recover. One of the things that happens whether it be aerobic or weight training is that cells in the body consume huge amounts of oxygen. That process, called oxidation, can damage cell membranes and impair their ability to function. Externally, how does this manifest? We’ve all been there…Muscle soreness, inflammation, and fatigue. What we’re going to talk about for the next few minutes is how to correct that and optimize the healing process.    I’m going to list 5 simple steps you can take to jump start the healing and recovery process: I’m a big believer in food as medicine. I love going right to the source and that’s food for nutrients but some of the things I’ll mention do come in supplement (capsule or powder) form but I’m going to mention the food source as well. -First up, Antioxidants – one you can use Quercetin  - found in apples, blueberries, and buckwheat herbal tea -Next, an Anti-inflammatant - Bromelain it’s an enzyme derived from pineapple you can get it either by drinking the juice or eating the fruit. It’s more concentrated at the core of the pineapple. So, if you’re slicing it up to eat….don’t toss the core! - How about Minerals…there’s a mineral that aids muscle recovery and it also calms the brain. It’s  Magnesium - available as a supplement, but naturally found in nuts (especially almonds and brazil nuts), seeds (such as pumpkin or flax), and legumes (those include beans, chickpeas and lentils). - Another important factor for rapid recovery is healthy Blood Glucose Homeostasis or balance there’s a natural spice that can help and it’s is Cinnamon. Based on recent studies it’s thought help with blood sugar control by increasing insulin sensitivity. This can allow the body to better perform tissue repair. Anywhere from about 1-6 grams of cinnamon has been used in clinical studies. How much does that equate to? Well 1 gram of ground cinnamon is about ½ a teaspoon. So, it doesn’t take much to reap the healthy benefits. - Last up, number 5: Rehydrate! – with what else…H2O - your body is roughly 55% water for women and 60% for men and you decrease your water stores through perspiration, cellular activity and metabolism during intense workouts. So drink up! To recap: 5 nutrients to aid body recovery       Antioxidants: Quercetin       Anti-inflammatant: Bromelain       Mineral: Magnesium       Blood Glucose balance: Cinnamon       Hydration: water   These easy steps will help you recover optimally post workout or race! KEY TERMS & IDEAS: During exercise our bodies consume a lot of oxygen That oxygen consumption contributes to post-exercise muscle soreness, inflammation, and fatigue You want to support the body’s healing process and repair mechanisms 5 nutrients and foods that provide balanced nourishment and support recovery: antioxidants (quercetin in blueberries), anti-inflammatants (bromelain in pineapple), mineral (magnesium in nuts), blood glucose balance (cinnamon), and HYDRATE! LINKS & RESOURCES: Follow Nada on LInkedin https://www.linkedin.com/in/nada-milosavljevic-35b502b9/ Sage Tonic www.sagetonic.com Sage Tonic on Instagram https://www.instagram.com/sagetonic/ “The lactate shuttle during exercise and recovery.” Medicine and Science in Sports and Exercise  Jun 1, 1986,18(3):360-368 https://europepmc.org/abstract/med/3523107 “Contextualising Maximal Fat Oxidation During Exercise: Determinants and Normative Values” Front Physiol. 2018;9:599 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974542/ “Properties and therapeutic application of bromelain: a review” Biotechnol Res Int. 2012; 2012: 976203. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529416/ “The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance” Diabetes Obes Metab. 2009 Dec;11(12):1100-13. https://www.ncbi.nlm.nih.gov/pubmed/19930003 SUBSCRIBE: Apple Podcasts: http://bit.ly/SpartanUpShow YouTube: http://bit.ly/SpartanUpYT Google Play: http://bit.ly/SpartanUpPlay   Nutrients for Rapid Recovery   // SPARTAN HEALTH ep 010 FOLLOW SPARTAN UP: Spartan Up on Instagram https://www.instagram.com/spartanuppodcast/ Spartan Up on Twitter https://twitter.com/SpartanUpPod   CREDITS: Producer: Marion Abrams, Madmotion, llc. Writer and Host: Nada Milosavljevic MD, JD   © 2018 Spartan  

Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab. 2015 Mar;17(3):268-75